crossing96/oncoscreening huggingface dataset:
BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG.	Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established and effective intravesical therapies are available for patients whose tumours recur after BCG, representing a clinically important unmet need. Development and discovery of treatment options for BCG-unresponsive NMIBC is a high priority in order to decrease the morbidity, burden of health-care expenditures, and mortality related to bladder cancer. This Review of treatment options after BCG failure focuses on principles of optimal management emerging therapies, thus enabling a synthesis of recommendations for management for such patients.	bladder
[The risk of bladder cancer in patients with prostatic hyperplasia and strategies to manage this combination].	The combination of bladder cancer with benign prostatic hyperplasia (BPH) occurs in 5-27% of cases. The link between these diseases has not yet been closely investigated. The main role in the pathogenesis of bladder cancer combined with BPH is played by the residual urine and prolonged exposure of urothelium to the urine carcinogens. The choice of surgical treatment modality for the combination of non-muscle invasive bladder cancer and BPH is still a matter of debate. There is no consensus on the safety and appropriateness of simultaneous transurethral resection of the bladder and prostate in these patients. On one hand, opponents of simultaneous surgery suggest sustained exposure to carcinogens and the spread of tumor cells in a transurethral resection through the prostate wound surface in the blood and lymphatic vessels. On the other hand, supporters refer to studies and meta-analyzes showing that the simultaneous resection neither increases the recurrence rate of bladder cancer nor causes metastasis and tumor progression.	bladder
[Point somatic mutations in bladder cancer: key carcinogenesis events, diagnostic markers and therapeutic targets].	Development of bladder cancer (BC) involves accumulating several genetic alterations in somatic cells: point mutations, extended deletions in the localization of tumor suppressor genes, amplification of oncogenes, aberrant DNA methylation, changes in the expression pattern of regulatory RNAs and numerous structural genes. From all of the above, point mutations have the greatest potential as diagnostic markers, as they frequently occur in carcinogenesis, characterize initiation and further clonal evolution of malignancy and represent a change in DNA detectable by routine molecular genetic methods. If we look at the clinical classification of bladder cancer, 90% of the BC presented by urothelial carcinoma, 80% of patients had superficial and 20% - of muscle-invasive tumors. The differences in morphological classification, staging and prognosis of bladder cancer represent different pathogenic pathways of tumor development. Superficial bladder cancer develops through a stage of hyperplasia involving activation of mutations in the genes FGFR3, PIK3CA, HRAS, ERBB2, TERT and others. It is shown that frequent point mutations FGFR3, PIK3CA and TERT are present in the tumor cells in the urine sediment and can be considered as markers for non-invasive molecular genetic diagnosis of primary BC and for monitoring of disease recurrence. Muscle-invasive bladder cancer develops through the stages of dysplasia and carcinoma in situ, in which mutations initially occur in key suppressor genes (TP53 and RB1) and a number of chromatin remodeling genes. This leads to genomic instability and multiple chromosome aberrations that are subjected to selection in the further clonal evolution of tumors towards predominance of more malignant subclones. This review presents systematized information about the main mutations in BC carcinogenesis, their role in the primary tumor progression, metastasizing and role as a target for diagnosis and targeted therapy.	bladder
Potential Utility of Diffusion-Weighted Magnetic Resonance Imaging in Diagnosis of Residual Bladder Cancer before Second Transurethral Resection.	INTRODUCTION: The study aimed to investigate the diagnostic utility of diffusion-weighted MRI (DW-MRI) in differentiating residual bladder cancer from benign postoperative changes before a second transurethral resection of the bladder (TURB). MATERIALS AND METHODS: Of the 75 bladder cancer patients who underwent a second TURB from 2013 to 2015, 23 patients who underwent multi-sequence bladder MRI after their initial TURB were retrospectively evaluated. Thirty lesions were histologically examined at the second TURB and the results of them were compared with the findings obtained through T2-weighted MRI, dynamic contrast-enhanced MRI (DCE-MRI), and DW-MRI. RESULTS: Positive findings of 27, 28, and 15 lesions showed up on T2W-, DCE-, and DW-MRI, respectively. Thirteen lesions were confirmed histologically to constitute residual cancer. The sensitivity/specificity/accuracy of T2W-, DCE-, and DW-MRI were 100/18/53, 100/12/50, and 92/82/87%, respectively. DW-MRI was significantly superior in specificity and accuracy to T2W- (p < 0.01 for both) and DCE-MRI (p < 0.01 for both). CONCLUSIONS: This study first showed the superiority of DW-MRI to T2W- and DCE-MRI in differentiating residual cancer before a second TURB.	bladder
External Validation and Optimization of International Consensus Clinical Target Volumes for Adjuvant Radiation Therapy in Bladder Cancer.	PURPOSE: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. METHODS AND MATERIALS: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review. Images with LRF were exported into a treatment planning system, and IC CTVs were contoured and evaluated for adequacy of coverage of each LRF with respect to both the patient and each of 6 pelvic subsites: common iliac (CI) region, obturator region (OR), external and internal iliac region, presacral region, cystectomy bed, or other pelvic site. Revisions to the IC contours were proposed based on the findings. RESULTS: Of the 52 patients with documented LRF, 13 (25%) had LRFs that were outside of the IC CTV involving 17 pelvic subsites: 5 near the CI CTV, 5 near the OR CTV, 1 near the external and internal iliac region, and 6 near the cystectomy bed. The 5 CI failures were located superior to the CTV, and the 5 OR failures were located medial to the CTV. Increasing the superior boundary of the CI to a vessel-based definition of the aortic bifurcation, as well as increasing the medial extension of the OR by an additional 9 mm, decreased the number of patients with LRF outside of the IC CTV to 7 (13%). CONCLUSIONS: Modified IC CTVs inclusive of a slight adjustment superiorly for the CI region and medially for the OR may reduce the risk of pelvic failure in patients treated with adjuvant radiation therapy.	bladder
Tolerability of Concurrent Chemoradiation Therapy With Gemcitabine (GemX), With and Without Prior Neoadjuvant Chemotherapy, in Muscle Invasive Bladder Cancer.	PURPOSE: The aim of this study is to assess the tolerability of concurrent chemoradiation therapy with gemcitabine (GemX) in muscle invasive bladder cancer following neoadjuvant chemotherapy (neoGemX) by use of patient- and provider-reported outcomes. METHODS AND MATERIALS: Seventy-eight patients were treated with GemX. Thirty-eight received prior neoadjuvant chemotherapy (NAC). Patients were prospectively assessed during treatment and at 6 weeks and 12 months after treatment completion. Radiation therapy was given to a total dose of 52.5 Gy in 20 fractions with weekly concurrent gemcitabine chemotherapy, 100 mg/m(2). Toxicity was assessed by the care provider and by a patient-reported outcome questionnaire collecting scores on the late effects in normal tissues-subjective, objective, management, and analytic scales and was statistically compared at baseline and 12 months, as well as between the neoGemX and GemX groups. RESULTS: The median duration of follow-up was 15.9 months. The radiation therapy completion rate was 95%, and 96% of patients completed at least 3 cycles of gemcitabine. Bowel toxicity of grade 3 or greater was reported in 7 of 38 patients (18%) in the neoGemX group and 5 of 25 (20%) in the GemX group. Three GemX and two neoGemX patients had grade 3 or greater urinary toxicity. Forty-nine patients completed questionnaires and were included in the analysis. Scores on the late effects in normal tissues-subjective, objective, management, and analytic scales showed an expected peak by week 4 of treatment. There was no statistically significant difference between mean scores at baseline and 12 months after treatment completion or between the neoGemX and GemX groups. CONCLUSIONS: This study demonstrates that GemX, alone or following NAC, has manageable toxicity and acceptable treatment completion rates. Allowing for small patient numbers and the nonrandomized nature of this study, these results do not suggest any additional toxicity from the use of NAC prior to GemX.	bladder
Enhanced expression of Programmed cell death 1 (PD-1) protein in benign vascular anomalies.	Programmed cell death 1 (PD-1) and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the United States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently has approved anti-PD-L1 blocker for treatment of metastatic urothelial cell carcinoma. However, the role that the immune system might have on benign tumours including vascular anomalies has received less attention. In this study, we evaluated PD-1 and PD-L1 expression on two benign vascular anomalies: infantile haemangiomas and venous malformations. Tissue microarrays (TMAs) from these two entities were stained for PD-1 and PD-L1 antibodies. Blood vessels from normal tissue were used as control. The endothelial cells in both infantile haemangioma and venous malformation showed high expression of PD-1 but were negative for PD-L1. Endothelial cells within the blood vessels in normal tissues were negative for both PD-1 and PD-L1. Our results showed over-expression of PD-1 in subsets of vascular anomalies, while PD-L1 was negative. This would raise the possibility of immunotherapy in benign vascular tumour when other options are exhausted.	bladder
Indication for early cystectomy in nonmuscle-invasive bladder cancer. Literature review.	CONTEXT: High-risk nonmuscle-invasive bladder cancer is a disease that includes a heterogeneous group of patients, for whom close follow-up is recommended due to the risk of progression to a muscle-invasive tumour. The treatment of choice for these tumours is transurethral resection of the bladder tumour followed by a programme of bacillus Calmette-Guerin instillations. There is a subgroup of patients who have a greater risk of progression and who benefit from early radical treatment. OBJECTIVE: To identify which patient group with nonmuscle-invasive bladder cancer will benefit from early radical treatment. SEARCHING THE EVIDENCE: We performed a literature review to identify the risk factors for progression for these patients and thereby recommend a treatment that improves their survival rate. SYNTHESIS OF THE EVIDENCE: We identified the various prognostic factors associated with tumour progression: the persistence of T1 tumour in re-resection of the bladder tumour, the presence of carcinoma in situ, patients refractory to bacillus Calmette-Guerin treatment, patients older than 70 years, tumours larger than 3cm, the substaging of T1 tumours, the presence of lymphovascular invasion and the presence of a tumour in the prostatic urethra. Similarly, we comment on the advantages of radical versus conservative treatment, considering that the performance of an early cystectomy due to a high-risk noninvasive vesical tumour has a better cancer prognosis than those in which the operation is deferred until the progression. CONCLUSIONS: In this disease, it is important to individualise the patients to provide them personalized treatment. For patients with the previously mentioned characteristics, it is recommended that early cystectomy not be delayed.	bladder
Poly - (l) - glutamic acid drug delivery system for the intravesical therapy of bladder cancer using WGA as targeting moiety.	In the management of bladder cancer, surgical resection of the tumour is usually followed by intravesical instillation of immunomodulatives and/or chemotherapeutics. The purpose of this local intravesical therapy is to eliminate residual malignant cells after surgical intervention. The main limitation of a localised adjuvant therapy is the insufficient concentration of the active pharmaceutical ingredient (API) in malignant cells due to the unique structure of the human urothelium making it an exclusively hard to overcome barrier in the human body. Different strategies such as electromotive drug administration or local hyperthermia are employed to ameliorate intravesical drug uptake. Previous studies on biorecognitive targeting showed promising results for lectin-, especially wheat germ agglutinin (WGA), mediated drug delivery. Here, we present a targeted conjugate that provides enough binding sites for a possible API as well as high cytoadhesive and cytoinvasive potential. The conjugate should comprise the following components: First WGA, as the targeting moiety, second poly-l-glutamic acid (PGA) as a polymeric backbone providing more than 300 possible binding sites for an API and third fluorescein cadaverine (Fc), a fluorescent dye we coupled to PGA rendering the conjugate traceable. After purification via size exclusion chromatography (SEC) the WGA containing and therefore binding conjugate was isolated from the reaction mix. In flow-cytometric and fluorimetric experiments with single cells and cell monolayers, respectively, binding and internalisation of the conjugate representing a high molecular weight (>100kDa) could be demonstrated. Fluorescent PGA without the WGA component showed neither binding nor internalisation potential. Microscopic colocalization studies with cell monolayers and single cells confirmed the cytoadhesive and cytoinvasive potential of the WGA containing conjugate. In accordance with the results of specificity studies the interaction between the conjugate and the cell surface depended solely on the WGA component of the conjugate. With the help of this targeted drug delivery system limiting factors of intravesical adjuvant therapy could eventually be overcome and thereby treatment efficacy of instillative chemotherapy could be improved. In addition, traceable drug conjugates might bear interesting advantages for theranostic purposes in the treatment of bladder cancer.	bladder
[Immunotherapy for the treatment of patients with genitourinary cancers: Review and perspectives].	Management of genitourinary (GU) cancers is improving rapidly with the development of immunotherapy agents, especially anti-PD-1/anti-PD-L1 therapies. Large studies have shown better outcomes for the treatment of these patients, leading to new drug approvals and recent changes in standards of care in renal, prostate and bladder cancer. We performed a review of recent studies assessing efficacy of immuno-oncology therapies in GU cancers. New results are summarized and next ways of development of clinical research are discussed as the use of such therapies will soon be assessed in first-line or adjuvant settings.	bladder
Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder.	Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. The precise diagnosis of MG has important implications on management, as treatment with steroids can transiently worsen myasthenia in nearly 50% of cases.	bladder
Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer.	CONTEXT: Pelvic organ-preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy (RC). OBJECTIVE: To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer. EVIDENCE ACQUISITION: Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single-arm case series were included. The primary outcomes were sexual function at 6-12 months after surgery and oncological outcomes including disease recurrence and overall survival (OS) at >2 years. Secondary outcomes included urinary continence at 6-12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment. EVIDENCE SYNTHESIS: The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched-pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients' sexual satisfaction score of 88.5 (80-100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow-up of between 12 and 132 months. At 3 and 5 years, cancer-specific survival was 70-100% and OS was 65-100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night-time continence rates were 58-100% and 42-100%, respectively. Overall, the self-catheterisation rate was 9.5-78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup-analysis, a narrative synthesis approach was used. The overall RoB was high across all studies. CONCLUSION: For well-selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC, oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting.	bladder
Diagnostic value of smoothelin and vimentin in differentiating muscularis propria from muscularis mucosa of bladder carcinoma.	BACKGROUND: Determination of the extent of involvement or pathological staging is one of the requirements for adequate evaluation of bladder cancer specimens. Therefore, the differentiation between MP and MM is essential for proper treatment and avoiding over or under staging. AIM: The present study aimed at evaluation of diagnostic value of smoothelin and vimentin expression both singly and in combination for differentiation between MM and MP. METHODS: This study was carried out on 59 cystectomy specimens of primary bladder carcinoma and eleven cystoscopic biopsies for non-neoplastic bladder lesions (cystitis). RESULTS: Histologically, MM was identified clearly in 40 cases and MP was identified in all 70 examined cases. The cases were immunostained for smoothelin and vimentin. Intensity of smoothelin expression showed significant difference (P = 0.001) between MM and MP with 97.5% sensitivity and 95% specificity and the percentage of smoothelin expression was significantly higher in MP compared to MM (P = 0.001) with 95.7% sensitivity and 85% specificity (using 65% as cut-off point). Vimentin was negative in MP and showed positive expression in 32 cases (80%) of MM with a statistical significant difference (P = 0.001) providing 80% sensitivity and 100% specificity. Combined moderate to strong smoothelin and negative vimentin offered 100% sensitivity and 100% specificity towards the identification of MP. CONCLUSIONS: Differentiation of MM from MP can be made based on histopathological criteria, which are unfortunately overlapping in many cases. Moderate to strong smoothelin expression with negative vimentin could be very helpful procedure in difficult and overlapping cases with a high diagnostic validity.	bladder
Impact of an enhanced recovery after surgery programme in radical cystectomy. A cohort-comparative study.	OBJECTIVE: To evaluate the results of the implementation of an enhanced recovery program (ERAS) for open approach radical cystectomy compared to the historical cohort of the same hospital. MATERIAL AND METHODS: A retrospective analysis of 138 consecutive patients who underwent radical cystectomy with Bricker or Studer ileal derivation (97 historical vs. 41 ERAS). Overall complication rate, Clavien-Dindo stage>2 complications, mortality, hospital and critical care length of stay and readmission rates, as well as need for reoperation, nasogastric intubation, transfusion or parenteral nutrition were compared. RESULTS: No statistically significant differences in overall complication rate were found (73.171 vs. 77.32%; OR 1.25, 95% CI 0.54-2.981; P=.601) nor in Clavien-Dindo>2 complications (41.463 vs. 42.268%; OR 1.033, 95% CI 0.492-2.167; P=.93), mortality, lengths of stays readmission and reoperation rates. The need for nasogastric tube insertion was lower in the ERAS group (43.902 vs. 78.351%; OR 4.624, 95% CI 2.112-10.123; P<.0001), as well as the need for total parenteral nutrition (26.829 vs. 34.021%; OR 12.234, 95% CI 5.165-28.92; P<.0001), and time under endotracheal intubation since anaesthesia induction (median [IRQ]=325 (285-355) vs. 540 (360-600) min; P<.0001). CONCLUSION: Enhanced recovery programs in radical cystectomy decrease interventionism on the patient without increasing morbidity and mortality.	bladder